So far, several methods of preparation of deferasirox of formula I have been described, which are listed in CZ patent No. 291470 based on WO 97/49395.
Method (a): Condensation reaction of benzoxazinone of formula II
with 4-hydrazinobenzoic acid of formula III
in polar solvents or mixtures of solvents, preferably in lower alcohols, with optional addition of a base if 4-hydraziobenzoic acid hydrochloride is used for the reaction under cooling conditions, at room temperature or at increased temperature up to the boiling temperature of the reaction mixture.
The starting compound of formula II can be prepared, for example, through a reaction of salicylic acid with salicylamide in the presence of thionyl chloride (Brunetti H., Lüthi C. E., Helvetica Chimica Acta, 55, 1566 (1972)).
Method (b): Reaction of 1,2,4-dithiazolidine of formula IV with 4-hydrazinobenzoic acid of formula III without a solvent or in a polar solvent or their mixtures under cooling conditions, at room temperature or at increased temperature.

Method (c): Reaction of the amide of formula V with 4-hydrazinobenzoic acid of formula III in a polar protic solvent under slightly acidic catalysis.

The above-mentioned methods of preparation suffer from the drawback of generating high quantities of impurities that decrease the yield of the reaction and impair the quality of the prepared deferasirox.
Since there are not given any yields or purities in the Examples of WO 97/49395, we have carried out several times thorough reproduction of Example 5. In the best case the yield of 57% and HPLC purity of 97% could be obtained; in a further attempt the yield was 68% but the purity was only 63% HPLC.